When to start children with Fabry disease on therapy is controversial because of its expense and inconvenience. Many Fabry children complain of exercise intolerance. In adults, the investigators have found decreased lung function and ability to exercise on a treadmill. Whether or not lung function and exercise capacity is abnormal in children is unknown. While lung function and exercise tests are commonly part of routine evaluations for adults with Fabry, they are not yet for children.

The objective of the proposed study is to more accurately define the lung and exercise abnormalities in a group of 20 boys from 8-18 years of age with Fabry disease who have not been treated with enzyme replacement therapy (Fabrazyme).

The maximum decrease in diastolic blood pressure with exercise will be compared to baseline diastolic blood pressure.

Estimated Enrollment:

20

Study Start Date:

April 2010

Detailed Description:

Fabry disease is due to an alteration in the genetic material (DNA) that causes a deficiency of the alpha-galactosidase A enzyme. This enzyme aids in the breakdown and elimination of certain types of fatty substances called glycolipids. These glycolipids are normally present within the body in most cells. When alpha-galactosidase A is lacking, these glycolipids build up in various tissues such as the eye, liver, kidney, skin, muscle, heart, and blood vessels. The build up of glycolipid levels in these tissues, particularly globotriaosylceramide (GL-3), is thought to cause the clinical symptoms that are associated with Fabry disease. Fabry disease causes chronic kidney damage leading to a need for dialysis or kidney transplantation, chronic heart damage leading to abnormal heart rhythms and heart attacks and strokes at an early age, nervous system damage leading to chronic pain, and a premature death. Because the gene for Fabry is on the X chromosome (men have only one X chromosome while women have two), most patients with symptoms of Fabry are men but many women have symptoms that may be as severe as men. There is currently a FDA approved treatment available that treats many of the symptoms of Fabry, but it involves intravenous infusions every other week and is very expensive.

When to start children on therapy is controversial because of its expense and inconvenience. Children with significant pain or gastrointestinal problems are started on therapy immediately, otherwise not until they are at least teenagers. Increasing evidence suggests that even without overt symptoms, significant, irreversible damage may be occurring in childhood. However, determining whether such damage is present or not requires biopsies. There are no simple measures of disease severity.

Many Fabry children complain of exercise intolerance. In adults, the investigators have found decreased lung function and ability to exercise on a treadmill. Whether or not lung function and exercise capacity is abnormal in children is unknown. While lung function and exercise tests are commonly part of routine evaluations for adults with Fabry, they are not yet for children.

The objective of the proposed study is to more accurately define the lung and exercise abnormalities in a group of 20 boys from 8-18 years of age with Fabry disease who have not been treated with enzyme replacement therapy (Fabrazyme). This will be done by several breathing tests and exercising on a treadmill. If the breathing tests are abnormal, then testing would serve as an easy way to evaluate children and help decide when therapy should be started and monitor the effectiveness of therapy.

Each person that consents to participate in the study will be required to commit to a single study visit that will last approximately 4 hours at Cedars-Sinai Medical Center. The participant will be expected to wear loose fit clothing and comfortable athletic footwear.

As part of the research, participants will be asked to participate in the following tests:

A pulmonary function test

Exercise test. Results will be forwarded to each participant's primary care physician.

All subjects must have previously been enrolled in the Fabry Registry and have the recommended standard of care assessments in order to be eligible for this pilot study.

Eligibility

Ages Eligible for Study:

8 Years to 18 Years

Genders Eligible for Study:

Male

Accepts Healthy Volunteers:

No

Sampling Method:

Non-Probability Sample

Study Population

Boys between ages 8 and 18 years of age with Fabry disease not receiving enzyme replacement therapy or an experimental therapy.

Criteria

Inclusion Criteria:

Fabry disease

Male

Between 8-18 years of age

Enrolled in Fabry registry and have standard assessments

Exclusion Criteria:

Enzyme replacement therapy or an experimental therapy

Inability to perform the tests

Other, serious medical conditions that would impact the tests

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01304875